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1.
J Abnorm Psychol ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599630

RESUMO

Age of first drink (AFD) has repeatedly been found to be associated with alcohol use disorder (AUD); however, some studies suggest this is a noncausal effect that may be due to childhood risk factors or familial influences. In contrast to indicators of any early alcohol use, such as AFD, indicators of a pattern of repeated drinking may be more likely to be causally associated with later problematic alcohol use. The current study examined AFD and age of onset of regular drinking (ARD; defined as drinking at least once a month for 6 or more months) as quasicausal predictors of lifetime AUD symptoms. Participants were 3,005 adult Australian twins who reported having been regular drinkers in their lifetime. Semistructured interviews were conducted to assess AFD, ARD, AUD, externalizing symptomatology, and other substance use. Personality traits were assessed via questionnaire. Unadjusted and adjusted multilevel discordant twin models were conducted using data from 1,041 complete twin pairs; adjusted models included socioeconomic status, personality, conduct disorder, and early initiation of regular smoking and marijuana use as covariates. Results from fully adjusted models controlling for familial confounds provided evidence for a causal influence of ARD on AUD symptoms, whereby twins with an earlier age of regular drinking than their cotwin had more lifetime AUD symptoms. However, AFD did not significantly predict AUD symptoms after adjusting for confounds. These results suggest that early regular drinking may serve as a causal risk factor for future problems, while early initiation of any alcohol use may indicate genetic liability. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

2.
Mol Psychiatry ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471575

RESUMO

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

3.
J Trace Elem Med Biol ; 57: 9-17, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31546210

RESUMO

BACKGROUND: Hip implants are usually manufactured from cobalt-chromium and titanium alloys. As the implants wear and corrode, metal debris is released into the surrounding tissue and blood, providing a potential biomarker for their function. Whilst there are laboratory reference levels for blood cobalt and chromium in patients with well and poorly functioning hip implants, there are no such guidelines for titanium. This is despite the increasing use of titanium implants worldwide. PATIENTS AND METHODS: We recruited a consecutive series of 95 patients (mean age 71 years, mean time after surgery 8.5 years) with one hip implant type, inserted by the same surgeon. We assessed clinical and radiological outcome, and measured blood and plasma titanium using high resolution inductively-coupled plasma mass spectrometry. RESULTS: The upper normal reference limit for blood and plasma titanium was 2.20 and 2.56 µg L-1, respectively, and did not differ significantly between males and females. CONCLUSION: We are the first to propose a laboratory reference level for blood and plasma titanium in patients with well-functioning titanium hip implants. This is an essential starting point for further studies to explore the clinical usefulness of blood titanium as a biomarker of orthopaedic implant performance, and comes at a time of considerable controversy regarding the use of certain titanium alloys in hip arthroplasty.

4.
Psychosom Med ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31469771

RESUMO

OBJECTIVE: Neuroticism is associated with poor health outcomes, but its contribution to the accumulation of health deficits in old age, i.e. the frailty index, is largely unknown. We aimed to explore associations between neuroticism and frailty cross-sectionally and longitudinally, and to investigate the contribution of shared genetic influences. METHOD: Data were derived from the UK Biobank (UKB, n=274,951), the Australian Over 50's Study (AO50, n=2,849) and the Swedish Twin Registry (SALT n=18,960, SATSA n=1,365). Associations between neuroticism and the frailty index were investigated using regression analysis cross-sectionally in UKB, AO50 and SATSA, and longitudinally in SALT (25-29y follow-up) and SATSA (6 and 23y follow-up). The co-twin control method was applied to explore the contribution of underlying shared familial factors (SALT, SATSA, AO50). Genome-wide polygenic risk scores for neuroticism were used in all samples to further assess whether common genetic variants associated with neuroticism predict frailty. RESULTS: High neuroticism was consistently associated with greater frailty cross-sectionally (adjusted ß [95% confidence intervals] in UKB=0.32[0.32-0.33]; AO50=0.35[0.31-0.39]; SATSA=0.33[0.27-0.39]) and longitudinally up to 29 years (SALT=0.24[0.22-0.25]; SATSA 6y=0.31[0.24-0.38]; SATSA 23y=0.16[0.07-0.25]). When adjusting for underlying shared genetic and environmental factors the neuroticism-frailty association remained significant, although decreased. Polygenic risk scores for neuroticism significantly predicted frailty in the two larger samples (meta-analyzed total ß=0.059[0.055-0.062]). CONCLUSION: Neuroticism in mid-life predicts frailty in late-life. Neuroticism may have a causal influence on frailty, whereas both environmental and genetic influences, including neuroticism-associated common genetic variants, contribute to this relationship.

5.
Twin Res Hum Genet ; 22(4): 210-219, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31379313

RESUMO

Twin registries often take part in large collaborative projects and are major contributors to genome-wide association (GWA) meta-analysis studies. In this article, we describe genotyping of twin-family populations from Australia, the Midwestern USA (Avera Twin Register), the Netherlands (Netherlands Twin Register), as well as a sample of mothers of twins from Nigeria to assess the extent, if any, of genetic differences between them. Genotyping in all cohorts was done using a custom-designed Illumina Global Screening Array (GSA), optimized to improve imputation quality for population-specific GWA studies. We investigated the degree of genetic similarity between the populations using several measures of population variation with genotype data generated from the GSA. Visualization of principal component analysis (PCA) revealed that the Australian, Dutch and Midwestern American populations exhibit negligible interpopulation stratification when compared to each other, to a reference European population and to globally distant populations. Estimations of fixation indices (FST values) between the Australian, Midwestern American and Netherlands populations suggest minimal genetic differentiation compared to the estimates between each population and a genetically distinct cohort (i.e., samples from Nigeria genotyped on GSA). Thus, results from this study demonstrate that genotype data from the Australian, Dutch and Midwestern American twin-family populations can be reasonably combined for joint-genetic analysis.

6.
Sci Rep ; 9(1): 11623, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31406173

RESUMO

Telomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10-6), methionine (p-value = 9.2 × 10-5), tyrosine (p-value = 2.1 × 10-4), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10-4), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10-4), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10-4). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality.

7.
Addiction ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31313399

RESUMO

BACKGROUND AND AIMS: The non-medical use of over-the-counter or prescribed analgesics (NMUA) is a significant public health problem. Little is known about the genetic and environmental etiology of NMUA and how these risks relate to other classes of substance use and misuse. Our aims were to estimate the heritability NMUA and sources of genetic and environmental covariance with cannabis and nicotine use, cannabis and alcohol use disorders and nicotine dependence in Australian twins. DESIGN: Biometrical genetic analyses or twin methods using structural equation univariate and multivariate modeling. SETTING: Australia. PARTICIPANTS: A total of 2007 young adult twins [66% female; µage  = 25.9, standard deviation (SD) = 3.6, range = 18-38] from the Brisbane Longitudinal Twin Study retrospectively assessed between 2009 and 2016. MEASUREMENTS: Self-reported NMUA (non-opioid or opioid-based), life-time nicotine, cannabis and opioid use, DSM-V cannabis and alcohol use disorders and the Fagerström Test for Nicotine Dependence. FINDINGS: Life-time NMUA was reported by 19.4% of the sample. Univariate heritability explained 46% [95% confidence interval (CI) = 0.29-0.57] of the risks in NMUA. Multivariate analyses revealed that NMUA is moderately associated genetically with cannabis (rg  = 0.41) and nicotine (rg  = 0.45) use and nicotine dependence (rg  = 0.34). In contrast, the genetic correlations with cannabis (rg  = 0.15) and alcohol (rg  = 0.07) use disorders are weak. CONCLUSIONS: In young male and female adults in Australia, the non-medical use of over-the-counter or prescribed analgesics appears to have moderate heritability. NMUA is moderately associated with cannabis and nicotine use and nicotine dependence. Its genetic etiology is largely distinct from that of cannabis and alcohol use disorders.

8.
Nat Neurosci ; 22(7): 1196, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168101

RESUMO

Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.

11.
Twin Res Hum Genet ; 22(3): 154-163, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31198126

RESUMO

The aim of the 25 and Up (25Up) study was to assess a wide range of psychological and behavioral risk factors behind mental illness in a large cohort of Australian twins and their non-twin siblings. Participants had already been studied longitudinally from the age of 12 and most recently in the 19Up study (mean age = 26.1 years, SD = 4.1, range = 20-39). This subsequent wave follows up these twins several years later in life (mean age = 29.7 years, SD = 2.2, range =  22-44). The resulting data set enables additional detailed investigations of genetic pathways underlying psychiatric illnesses in the Brisbane Longitudinal Twin Study (BLTS). Data were collected between 2016 and 2018 from 2540 twins and their non-twin siblings (59% female, including 341 monozygotic complete twin-pairs, 415 dizygotic complete pairs and 1028 non-twin siblings and singletons). Participants were from South-East Queensland, Australia, and the sample was of predominantly European ancestry. The 25Up study collected information on 20 different mental disorders, including depression, anxiety, substance use, psychosis, bipolar and attention-deficit hyper-activity disorder, as well as general demographic information such as occupation, education level, number of children, self-perceived IQ and household environment. In this article, we describe the prevalence, comorbidities and age of onset for all 20 examined disorders. The 25Up study also assessed general and physical health, including physical activity, sleep patterns, eating behaviors, baldness, acne, migraines and allergies, as well as psychosocial items such as suicidality, perceived stress, loneliness, aggression, sleep-wake cycle, sexual identity and preferences, technology and internet use, traumatic life events, gambling and cyberbullying. In addition, 25Up assessed female health traits such as morning sickness, breastfeeding and endometriosis. Furthermore, given that the 25Up study is an extension of previous BLTS studies, 86% of participants have already been genotyped. This rich resource will enable the assessment of epidemiological risk factors, as well as the heritability and genetic correlations of mental conditions.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31135366

RESUMO

Genome-wide association studies (GWAS) link full genome data to a handful of traits. However, in neuroimaging studies, there is an almost unlimited number of traits that can be extracted for full image-wide big data analyses. Large populations are needed to achieve the necessary power to detect statistically significant effects, emphasizing the need to pool data across multiple studies. Neuroimaging consortia, e.g., ENIGMA and CHARGE, are now analyzing MRI data from over 30,000 individuals. Distributed processing protocols extract harmonized features at each site, and pool together only the cohort statistics using meta analysis to avoid data sharing. To date such MRI projects have focused on single measures such as hippocampal volume, yet voxelwise analyses (e.g., tensor-based morphometry; TBM) may help better localize statistical effects. This can lead to 1013 tests for GWAS and become underpowered. We developed an analytical framework for multi-site TBM by performing multi-channel registration to cohort-specific templates. Our results highlight the reliability of the method and the added power over alternative options while preserving single site specificity and opening the doors for well-powered image-wide genome-wide discoveries.

13.
Psychol Addict Behav ; 33(4): 420-429, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31094546

RESUMO

The Diagnostic and Statistical Manual of Mental Disorders (DSM; 5th ed.) reassignment of gambling disorder as an addictive disorder alongside the substance-related addictive disorders encourages research into their shared etiologies. The aims of this study were to examine: (a) the associations of Big Five personality dimensions with alcohol, nicotine, cannabis, and gambling disorders, (b) the comorbidity between these disorders, (c) the extent to which common personality underpinnings explain comorbidity, (d) whether results differed for men and women, and (e) the magnitude of personality differences corresponding to the 4 disorders. Participants were 3,785 twins and siblings (1,365 men, 2,420 women; Mage = 32 years, range = 21-46 years) from the Australian Twin Registry who completed psychiatric interviews and Big Five personality inventories. The personality profile of high neuroticism, low agreeableness, and low conscientiousness was associated with all 4 addictive disorders. All but 1 of the pairwise associations between the disorders were significant. After accounting for Big Five traits, the associations were attenuated to varying degrees but remained significant. The results were generally similar for men and women. The results suggest that the Big Five traits of neuroticism, agreeableness, and conscientiousness are associated with the general propensity to develop an addictive disorder and may in part explain their co-occurrence; however, they may be more broadly associated with the propensity for any psychiatric disorder. The effect sizes of the personality associations suggest that the diagnosis of gambling disorder as operationalized by the DSM may be more severe than the other addictive disorders. Calibration of the diagnosis of gambling disorder to the other addictive disorders may be warranted. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Comportamento Aditivo/psicologia , Jogo de Azar/psicologia , Personalidade , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Austrália/epidemiologia , Comportamento Aditivo/epidemiologia , Comorbidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Jogo de Azar/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto Jovem
14.
Alcohol Clin Exp Res ; 43(6): 1103-1112, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31063677

RESUMO

BACKGROUND: Individuals differ in their sensitivity to alcohol's physiological effects, including blacking and passing out. Blackouts are periods of impaired memory formation when an individual engages in activities they later cannot recall, while passing out results in loss of consciousness. METHODS: The sample consisted of 3,292 adult twins from the Australian Twin Registry. Univariate twin analyses were conducted to examine the contributions of genetic and environmental influences to blacking and passing out occurrence and susceptibility (accounting for frequency of intoxication). Evidence for shared etiology of susceptibility to blacking and passing out was examined using bivariate twin analyses. RESULTS: Although blacking and passing out were strongly associated (odds ratio (OR) = 4.45, 95% confidence interval (CI): [3.85, 5.14]), the genetic epidemiology was quite different. Genetic (43%) and nonshared environmental (57%) influences contributed to liability for blackout occurrence. For passing out occurrence, there was evidence of sex differences. Among men, genetic (32%) and nonshared environmental (68%) influences contributed, whereas among women, there were shared (29%) and nonshared environmental (72%) influences. After accounting for frequency of intoxication, genetic influences on blackout susceptibility remained significant; in contrast, only nonshared environmental influences were significant for passing out susceptibility. There was evidence for overlapping genetic and nonshared environmental factors influencing susceptibility to blacking and passing out among men; among women, there were overlapping nonshared environmental influences. CONCLUSIONS: Blacking and passing out are 2 common sedative-like effects of heavy drinking, and people differ considerably in their susceptibility to these effects. This study suggests that differences in blackout susceptibility can be explained by genetic factors in both men and women, while differences in susceptibility to pass out after consuming alcohol may be attributable to environmental influences, particularly among women. These environmental factors may include changing social and cultural norms about alcohol use, drinking context, and the type(s) of alcohol consumed.

15.
Psychol Med ; 49(7): 1218-1226, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30929657

RESUMO

BACKGROUND: Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC. METHODS: Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals). RESULTS: Positive genetic correlation was observed between MD and AD (rgMD-AD = + 0.47, P = 6.6 × 10-10). AC-quantity showed positive genetic correlation with both AD (rgAD-AC quantity = + 0.75, P = 1.8 × 10-14) and MD (rgMD-AC quantity = + 0.14, P = 2.9 × 10-7), while there was negative correlation of AC-frequency with MD (rgMD-AC frequency = -0.17, P = 1.5 × 10-10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10-6). There was no evidence for reverse causation. CONCLUSION: This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.

16.
Am J Clin Nutr ; 109(6): 1724-1737, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31005972

RESUMO

BACKGROUND: Individual differences in human perception of sweetness are partly due to genetics; however, which genes are associated with the perception and the consumption of sweet substances remains unclear. OBJECTIVE: The aim of this study was to verify previous reported associations within genes involved in the peripheral receptor systems (i.e., TAS1R2, TAS1R3, and GNAT3) and reveal novel loci. METHODS: We performed genome-wide association scans (GWASs) of the perceived intensity of 2 sugars (glucose and fructose) and 2 high-potency sweeteners (neohesperidin dihydrochalcone and aspartame) in an Australian adolescent twin sample (n = 1757), and the perceived intensity and sweetness and the liking of sucrose in a US adult twin sample (n = 686). We further performed GWASs of the intake of total sugars (i.e., total grams of all dietary mono- and disaccharides per day) and sweets (i.e., handfuls of candies per day) in the UK Biobank sample (n = ≤174,424 white-British individuals). All participants from the 3 independent samples were of European ancestry. RESULTS: We found a strong association between the intake of total sugars and the single nucleotide polymorphism rs11642841 within the FTO gene on chromosome 16 (P = 3.8 × 10-8) and many suggestive associations (P < 1.0 × 10-5) for each of the sweet perception and intake phenotypes. We showed genetic evidence for the involvement of the brain in both sweet taste perception and sugar intake. There was limited support for the associations with TAS1R2, TAS1R3, and GNAT3 in all 3 European samples. CONCLUSIONS: Our findings indicate that genes additional to those involved in the peripheral receptor system are also associated with the sweet taste perception and intake of sweet-tasting foods. The functional potency of the genetic variants within TAS1R2, TAS1R3, and GNAT3 may be different between ethnic groups and this warrants further investigations.

17.
Nat Commun ; 10(1): 1052, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30837455

RESUMO

Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e-483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics support many of these findings. In silico functional analyses provide evidence for a role of T cell regulation in the aetiology of mouth ulcers. These results provide novel insight into the pathogenesis of a common, important condition.


Assuntos
Loci Gênicos/imunologia , Predisposição Genética para Doença , Fatores Imunológicos/genética , Úlceras Orais/genética , Estomatite Aftosa/genética , Adulto , Idoso , Estudos de Coortes , Simulação por Computador , Feminino , Estudo de Associação Genômica Ampla , Humanos , Fatores Imunológicos/imunologia , Masculino , Pessoa de Meia-Idade , Úlceras Orais/imunologia , Estomatite Aftosa/imunologia , Linfócitos T/imunologia
18.
Behav Genet ; 49(4): 386-398, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30877414

RESUMO

This study assessed the heritability of 25 hydroxyvitamin D3 (25(OH)D3) in a large twin cohort and the shared effect of sun exposure and skin colour on 25(OH)D3 variance. Study participants included 1604 twin pairs and their siblings (n = 4020). Twin correlations for 25(OH)D3 concentration were rMZ=0.79 (584 pairs) and rDZ = 0.52 (1020 pairs) consistent with an average h2 = 0.50 throughout the year. Significant phenotypic and genetic seasonal fluctuation was observed in 25(OH)D3 concentrations with heritability decreasing during the winter (h2 = 0.37) compared to summer (h2 = 0.62). Skin colour (measured both ordinally and quantitatively) and self-reported sun exposure were found to significantly affect 25(OH)D3 concentration. Twins with olive/dark skin had significantly lower 25(OH)D3 concentrations than those with fair/pale skin and multivariate genetic analysis showed that approximately half of the total additive genetic variation in 25(OH)D3 results from genes whose primary influence is on skin colour and sun exposure. Additionally, 37% of the total variance was attributed to shared environmental effects on vitamin D, skin colour and sun exposure measures. These results support a moderate estimate of vitamin D heritability and suggest significant influence of season, skin colour and sun exposure on the genetic variance.

19.
Drug Alcohol Depend ; 197: 271-279, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30875648

RESUMO

BACKGROUND: Co-morbid substance use is very common. Despite a historical focus using genetic epidemiology to investigate comorbid substance use and misuse, few studies have examined substance-substance associations using polygenic risk score (PRS) methods. METHODS: Using summary statistics from the largest substance use GWAS to date (258,797- 632,802 subjects), GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN), we constructed PRSs for smoking initiation (PRS-SI), age of initiation of regular smoking (PRS-AI), cigarettes per day (PRS-CPD), smoking cessation (PRS-SC), and drinks per week (PRS-DPW). We then estimated the fixed effect of individual PRSs on 22 lifetime substance use and substance use disorder phenotypes collected in an independent sample of 2463 young Australian adults using genetic restricted maximal likelihood (GREML) in Genome-wide Complex Trait Analysis (GCTA), separately in females, males and both sexes together. RESULTS: After accounting for multiple testing, PRS-SI significantly explained variation in the risk of cocaine (0.67%), amphetamine (1.54%), hallucinogens (0.72%), ecstasy (1.66%) and cannabis initiation (0.97%), as well as DSM-5 alcohol use disorder (0.72%). PRS-DPW explained 0.75%, 0.59% and 0.90% of the variation of cocaine, amphetamine and ecstasy initiation respectively. None of the 22 phenotypes including emergent classes of substance use were significantly predicted by PRS-AI, PRS-CPD, and PRS-SC. CONCLUSIONS: To our knowledge, this is the first study to report significant genetic overlap between the polygenic risks for smoking initiation and alcohol consumption and the risk of initiating major classes of illicit substances. PRSs constructed from large discovery GWASs allows the detection of novel genetic associations.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Herança Multifatorial , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Uso de Tabaco/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/genética , Alcoolismo/epidemiologia , Alcoolismo/genética , Austrália/epidemiologia , Comorbidade , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Fenótipo , Fatores de Risco , Fumar/epidemiologia , Fumar/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Uso de Tabaco/genética , Adulto Jovem
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